Journal
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
Volume 1825, Issue 1, Pages 29-36Publisher
ELSEVIER
DOI: 10.1016/j.bbcan.2011.10.001
Keywords
Gelatinase; Cell surface binding; Cancer; Inhibitor; Function; Outside-in signaling
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Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
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This review focuses on matrix metalloproteinases (MMPs)-2 (gelatinase A) and -9 (gelatinase B), both of which are cancer-associated, secreted, zinc-dependent endopeptidases. Gelatinases cleave many different targets (extracellular matrix, cytokines, growth factors, chemokines and cytokine/growth factor receptors) that in turn regulate key signaling pathways in cell growth, migration, invasion, inflammation and angiogenesis. Interactions with cell surface integral membrane proteins (CD44, aV beta/a beta 1/a beta 2 integrins and Ku protein) can occur through the gelatinases' active site or hemopexin-like C-terminal domain. This review evaluates the recent literature on the non-enzymatic, signal transduction roles of surface-bound gelatinases and their subsequent effects on cell survival, migration and angiogenesis. Gelatinases have long been drug targets. The current status of gelatinase inhibitors as anticancer agents and their failure in the clinic is discussed in light of these new data on the gelatinases' roles as cell surface transducers data that may lead to the design and development of novel, gelatinase-targeting inhibitors. (C) 2011 Elsevier B.V. All rights reserved.
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